The goal of this project is to locate and define the mechanisms involved in the production and regulation of cerebrospinal fluid (CSF). In vitro preparations of the choroid plexuses and the arachnoid will be used to study 1) the maintenance of the blood-CSF barrier, 2) the mechanism of CSF secretion and its control, and 3) the active transport of drugs and metabolites between the CSF and blood. Electrophysiological, radioactive tracer and biochemical experiments will be used to study the Na/K pump in the brush border of the choroid plexus epithelium and the interrelationships between the Na/K pump, adenylate and guanylate cyclases and humoral and neural agents. The agents will be reconciled with the literature on the control of CSF secretion by hormones and neural agents. The transport of drugs and metabolites between the CSF and blood across the arachnoid and choroid plexus will be investigated using radioactive tracer techniques. Particular emphasis will be placed on those substances which are implicated with a role in mental illness, e.g., 5 hydroxyindoleacetic acid. The influence of psychoactive agents (e.g. Li) on the various transport systems in the plexus and arachnoid will be explored to determine whether or not the blood-CSF barrier is a key factor in disorders of the nervous system.